TriangleNCT01136733 · OUTCOME
Phase 2: Progression-Free Survival (PFS)
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- MEDIAN
- Unit
- Months
- Interval / dispersion
- 95% Confidence Interval
- Time frame
- Date of randomization into Phase 2 (Cycle 1 Day 1) to the date of first documentation of disease progression or death (whichever occurred first), assessed up to data cutoff date (13 Jun 2014), up to approximately 2 years and 3 months
What was measured
PFS was defined as the time (in months) from the date of first dose of study drug to the first documentation of disease progression or death, whichever occurred first. Kaplan-Meier (K-M) estimates were used to estimate median PFS, presented with 2-sided 95% confidence intervals (CIs). Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease using computed tomography (CT) or magnetic resonance imaging (MRI) and scan acquisition techniques (including use or nonuse of intravenous (IV) contrast). Tumor response was determined at the site by the investigator and radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in the evaluation of the tumor assessment scans. The date of objective disease progression was defined as the earliest date of radiological disease progression. Participants removed from therapy due to clinical progression with no radiologic confirmation were censored at their last radiologic assessment date.
Analysis population: Full analysis set included all randomized participants.
Groups in this outcome
Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus
Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2. If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3. If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus
Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4. If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus
The DLT was achieved and no participants were enrolled into this cohort.
Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus
Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
Phase 2 (Arm B): 24 mg Lenvatinib
Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
Phase 2 (Arm C): 10 mg Everolimus
Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
| Group | Source count |
|---|---|
| Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus | 0 |
| Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus | 0 |
| Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus | 0 |
| Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus | 0 |
| Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus | 51 |
| Phase 2 (Arm B): 24 mg Lenvatinib | 52 |
| Phase 2 (Arm C): 10 mg Everolimus | 50 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus | 14.6 | Not reported | 5.9 | 20.1 | Not reported |
| Phase 2 (Arm B): 24 mg Lenvatinib | 7.4 | Not reported | 5.6 | 10.2 | Not reported |
| Phase 2 (Arm C): 10 mg Everolimus | 5.5 | Not reported | 3.5 | 7.1 | Not reported |
Source statistical analyses
- ci Lower Limit
- 0.24
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.68
- estimate Comment
- Hazard ratio between treatment groups and corresponding 95% CI was estimated using the stratified Cox regression model (stratified by hemoglobin and corrected serum calcium) with treatment as a factor.
- group Description
- Null hypothesis of no difference in PFS was analyzed using the stratified log-rank test with hemoglobin (less than or equal to 13 g/dL vs greater than 13 g/dL for males; and less than or equal to 11.5 g/dL vs greater than 11.5 g/dL for females) and corrected serum calcium (greater than or equal to 10 mg/dL vs less than 10 mg/dL) as stratification factors. Each null hypothesis was tested at a nominal alpha=0.05.
- group Ids
- OG004
- OG006
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- =0.0005
- param Type
- Hazard Ratio (HR)
- param Value
- 0.40
- statistical Method
- Log Rank
- ci Lower Limit
- 0.38
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.98
- group Ids
- OG005
- OG006
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- 0.0479
- param Type
- Hazard Ratio (HR)
- param Value
- 0.61
- statistical Method
- Log Rank
- ci Lower Limit
- 0.39
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.10
- group Ids
- OG004
- OG005
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- 0.1209
- param Type
- Hazard Ratio (HR)
- param Value
- 0.66
- statistical Method
- Log Rank
Complete source fields
- analyses
- ci Lower Limit
- 0.24
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.68
- estimate Comment
- Hazard ratio between treatment groups and corresponding 95% CI was estimated using the stratified Cox regression model (stratified by hemoglobin and corrected serum calcium) with treatment as a factor.
- group Description
- Null hypothesis of no difference in PFS was analyzed using the stratified log-rank test with hemoglobin (less than or equal to 13 g/dL vs greater than 13 g/dL for males; and less than or equal to 11.5 g/dL vs greater than 11.5 g/dL for females) and corrected serum calcium (greater than or equal to 10 mg/dL vs less than 10 mg/dL) as stratification factors. Each null hypothesis was tested at a nominal alpha=0.05.
- group Ids
- OG004
- OG006
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- =0.0005
- param Type
- Hazard Ratio (HR)
- param Value
- 0.40
- statistical Method
- Log Rank
- ci Lower Limit
- 0.38
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.98
- group Ids
- OG005
- OG006
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- 0.0479
- param Type
- Hazard Ratio (HR)
- param Value
- 0.61
- statistical Method
- Log Rank
- ci Lower Limit
- 0.39
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.10
- group Ids
- OG004
- OG005
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- 0.1209
- param Type
- Hazard Ratio (HR)
- param Value
- 0.66
- statistical Method
- Log Rank
- classes
- categories
- measurements
- group Id
- OG004
- lower Limit
- 5.9
- upper Limit
- 20.1
- value
- 14.6
- group Id
- OG005
- lower Limit
- 5.6
- upper Limit
- 10.2
- value
- 7.4
- group Id
- OG006
- lower Limit
- 3.5
- upper Limit
- 7.1
- value
- 5.5
- denoms
- counts
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 0
- group Id
- OG002
- value
- 0
- group Id
- OG003
- value
- 0
- group Id
- OG004
- value
- 51
- group Id
- OG005
- value
- 52
- group Id
- OG006
- value
- 50
- units
- Participants
- description
- PFS was defined as the time (in months) from the date of first dose of study drug to the first documentation of disease progression or death, whichever occurred first. Kaplan-Meier (K-M) estimates were used to estimate median PFS, presented with 2-sided 95% confidence intervals (CIs). Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease using computed tomography (CT) or magnetic resonance imaging (MRI) and scan acquisition techniques (including use or nonuse of intravenous (IV) contrast). Tumor response was determined at the site by the investigator and radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in the evaluation of the tumor assessment scans. The date of objective disease progression was defined as the earliest date of radiological disease progression. Participants removed from therapy due to clinical progression with no radiologic confirmation were censored at their last radiologic assessment date.
- dispersion Type
- 95% Confidence Interval
- groups
- description
- Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2. If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
- id
- OG000
- title
- Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus
- description
- Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3. If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
- id
- OG001
- title
- Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus
- description
- Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4. If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
- id
- OG002
- title
- Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus
- description
- The DLT was achieved and no participants were enrolled into this cohort.
- id
- OG003
- title
- Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus
- description
- Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
- id
- OG004
- title
- Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus
- description
- Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
- id
- OG005
- title
- Phase 2 (Arm B): 24 mg Lenvatinib
- description
- Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
- id
- OG006
- title
- Phase 2 (Arm C): 10 mg Everolimus
- param Type
- MEDIAN
- population Description
- Full analysis set included all randomized participants.
- reporting Status
- POSTED
- time Frame
- Date of randomization into Phase 2 (Cycle 1 Day 1) to the date of first documentation of disease progression or death (whichever occurred first), assessed up to data cutoff date (13 Jun 2014), up to approximately 2 years and 3 months
- title
- Phase 2: Progression-Free Survival (PFS)
- type
- PRIMARY
- unit Of Measure
- Months
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Preserved source evidence · Not medical advice